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Evidence for a prepore stage in the action of clostridium perfringens epsilon toxin

Robertson, SL and Li, J and Uzal, FA and McClane, BA (2011) Evidence for a prepore stage in the action of clostridium perfringens epsilon toxin. PLoS ONE, 6 (7).

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Abstract

Clostridium perfringens epsilon toxin (ETX) rapidly kills MDCK II cells at 37°C, but not 4°C. The current study shows that, in MDCK II cells, ETX binds and forms an oligomeric complex equally well at 37°C and 4°C but only forms a pore at 37°C. However, the complex formed in MDCK cells treated with ETX at 4°C has the potential to form an active pore, since shifting those cells to 37°C results in rapid cytotoxicity. Those results suggested that the block in pore formation at 4°C involves temperature-related trapping of ETX in a prepore intermediate on the MDCK II cell plasma membrane surface. Evidence supporting this hypothesis was obtained when the ETX complex in MDCK II cells was shown to be more susceptible to pronase degradation when formed at 4°C vs. 37°C; this result is consistent with ETX complex formed at 4°C remaining present in an exposed prepore on the membrane surface, while the ETX prepore complex formed at 37°C is unaccessible to pronase because it has inserted into the plasma membrane to form an active pore. In addition, the ETX complex rapidly dissociated from MDCK II cells at 4°C, but not 37°C; this result is consistent with the ETX complex being resistant to dissociation at 37°C because it has inserted into membranes, while the ETX prepore readily dissociates from cells at 4°C because it remains on the membrane surface. These results support the identification of a prepore stage in ETX action and suggest a revised model for ETX cytotoxicity, i) ETX binds to an unidentified receptor, ii) ETX oligomerizes into a prepore on the membrane surface, and iii) the prepore inserts into membranes, in a temperature-sensitive manner, to form an active pore. © 2011 Robertson et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Robertson, SL
Li, Jjihongli@pitt.eduJIHONGLI
Uzal, FA
McClane, BAbamcc@pitt.eduBAMCC
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorRatner, Adam J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 14 July 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0022053
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
MeSH Headings: Animals; Bacterial Toxins--toxicity; Brain--cytology; Brain--drug effects; Brain--metabolism; Cell Membrane--drug effects; Cell Membrane--metabolism; Cells, Cultured; Clostridium perfringens; Dogs; Kidney--cytology; Kidney--drug effects; Kidney--metabolism; Mice; Protein Binding
Other ID: NLM PMC3140917
PubMed Central ID: PMC3140917
PubMed ID: 21814565
Date Deposited: 05 Sep 2012 17:46
Last Modified: 02 Feb 2019 16:58
URI: http://d-scholarship.pitt.edu/id/eprint/13875

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